Martinuzzi Andrea, Liava Alexandra, Trevisi Enrico, Frare Mara, Tonon Caterina, Malucelli Emil, Manners David, Kemp Graham J, Testa Claudia, Barbiroli Bruno, Lodi Raffaele
E. Medea Scientific Institute, Conegliano Research Centre, via Costa Alta 37, 31015 Conegliano (TV), Italy.
Muscle Nerve. 2008 Mar;37(3):350-7. doi: 10.1002/mus.20937.
McArdle's disease causes limitation in exercise capacity as well as disability, the severity of which has been associated with the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) haplotype-patients with the genotype associated with higher ACE activity show the most severe phenotype. Modulation of ACE activity through the use of inhibitors may thus positively affect disease expression. In a double-blind, randomized, placebo-controlled trial, we assessed the efficacy of an ACE inhibitor (2.5 mg ramipril) in 8 patients with McArdle's disease. End-points were changes in parameters of exercise physiology (cycloergometer and muscle 31P-magnetic resonance spectroscopy), quality of life (QoL) according to the Short Form 36 (SF-36), and disability according to the World Health Organization-Disability Assessment Scale II (WHO-DAS II). Patients had lower QoL and higher disability than controls. Measures of exercise physiology were not changed by ramipril in the whole group, but treatment induced higher peak VO2 (P = 0.017) in ACE D/D patients, yet not in I/D patients. Treatment significantly improved disability (P < 0.05). McArdle's disease is a disabling condition affecting patients' QoL. Treatment with ramipril improves disability and modifies exercise physiology only in D/D patients, raising the possibility of a differential haplotype-linked sensitivity to the treatment.
麦克尔迪氏病会导致运动能力受限以及残疾，其严重程度与血管紧张素转换酶（ACE）插入（I）/缺失（D）单倍型有关——具有与较高ACE活性相关基因型的患者表现出最严重的表型。因此，通过使用抑制剂调节ACE活性可能会对疾病表现产生积极影响。在一项双盲、随机、安慰剂对照试验中，我们评估了一种ACE抑制剂（2.5毫克雷米普利）对8例麦克尔迪氏病患者的疗效。终点指标包括运动生理学参数（蹬车测力计和肌肉31P磁共振波谱）的变化、根据简明健康调查问卷36项版本（SF-36）得出的生活质量（QoL）以及根据世界卫生组织残疾评定量表第二版（WHO-DAS II）得出的残疾情况。患者的生活质量低于对照组，残疾程度高于对照组。雷米普利对整个组的运动生理学指标没有影响，但治疗使ACE D/D型患者的峰值摄氧量升高（P = 0.017），而I/D型患者则没有。治疗显著改善了残疾情况（P < 0.05）。麦克尔迪氏病是一种影响患者生活质量的致残性疾病。雷米普利治疗仅改善了D/D型患者的残疾情况并改变了其运动生理学，这增加了不同单倍型对治疗敏感性存在差异的可能性。
